Humanized nonobese diabetic-scid IL2r[gamma]^sup null^ mice are susceptible to lethal Salmonella Typhi infection

Salmonella enterica serovar Typhi, the cause of typhoid fever, is host-adapted to humans and unable to cause disease in mice. Here, we show that S. Typhi can replicate in vivo in nonobese diabetic (NOD)-scid IL2r... mice engrafted with human hematopoietic stem cells (hu-SRC-SCID mice) to cause a let...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-08, Vol.107 (35), p.15589
Main Authors: Libby, Stephen J, Brehm, Michael A, Greiner, Dale L, Shultz, Leonard D, McClelland, Michael, Smith, Kelly D, Cookson, Brad T, Karlinsey, Joyce E, Kinkel, Traci L, Porwollik, Steffen, Canals, Rocio, Cummings, Lisa A, Fang, Ferric C
Format: Article
Language:English
Subjects:
Bacterial infections
Deoxyribonucleic acid
Diabetes
DNA
Pathogenesis
Pathology
Rodents
Salmonella
Typhoid
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Summary:Salmonella enterica serovar Typhi, the cause of typhoid fever, is host-adapted to humans and unable to cause disease in mice. Here, we show that S. Typhi can replicate in vivo in nonobese diabetic (NOD)-scid IL2r... mice engrafted with human hematopoietic stem cells (hu-SRC-SCID mice) to cause a lethal infection with pathological and inflammatory cytokine responses resembling human typhoid. In contrast, S. Typhi does not exhibit net replication or cause illness in nonengrafted or immunocompetent control animals. Screening of transposon pools in hu-SRC-SCID mice revealed both known and previously unknown Salmonella virulence determinants, including Salmonella Pathogenicity Islands 1, 2, 3, 4, and 6. Our observations indicate that the presence of human immune cells allows the in vivo replication of S. Typhi in mice. The hu-SRC-SCID mouse provides an unprecedented opportunity to gain insights into S. Typhi pathogenesis and devise strategies for the prevention of typhoid fever. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0027-8424
1091-6490